Use of corticosteroid is not associated with improved outcomes in idiopathic pulmonary fibrosis (IPF) patients admitted to the hospital with acute exacerbation (AE), reveals a recent study. In addition, corticosteroids may even contribute to reduced overall survival following exacerbation.

Acne is a common skin problem seen in primary care. Dr Wong
Soon Tee of Assurance Skin Clinic at Mt Elizabeth Novena Hospital, Singapore
shares his insights with Pearl Toh on how to manage acne in the primary care
setting.

10 treatments for COVID-19: What works and what does not?

Stephen Padilla

01 May 2020

There is currently no approved treatment for the novel coronavirus disease (COVID-19) because of lack of evidence, but several clinical trials are being carried out across the globe to find a cure in the soonest time possible.

To keep track of the latest developments in the field, Waquar Ahsan and colleagues from Jazan University in Saudi Arabia have initiated a review of various approaches of COVID-19 treatment and of some of the most recent clinical trials in process. [Drug Discov Ther 2020;doi:10.5582/ddt.2020.03008]

“A number of trials have been and are being conducted to come up with a drug which shows significant efficacy and safety in the treatment of COVID-19,” the researchers said. “Few have shown encouraging results, and few are in pipeline.”

Here’s a short list of 10 potential treatments for COVID-19:

1. Convalescent Plasma – The plasma of recovered patients may help treat those with severe COVID-19 as it contains antibodies developed by the body in response to the viral infection. A clinical trial carried out between 23 January 2020 and 19 February 2020 reported five of 10 patients showing rapid increase in the antibody titre values to 1:640, while the other four also demonstrated high titre values. Clinical symptoms significantly improved, including better oxyhaemoglobin saturation, increased lymphocytes count and reduced level of C-reactive protein with no adverse effects. [PNAS 2020;117:9490-9496]

2. Chloroquine (CQ) and Hydroxychloroquine (HCQ) – CQ is originally used as an antimalarial drug. In vitro studies conducted recently found that CQ inhibited SARS-Cov-2, the virus that causes COVID-19, at EC50 1.13 µM and CC50 >100 µM. There are at least 16 trials registered to examine the efficacy and safety of CQ and HCQ in the treatment of COVID-19 patients. [Cell Res 2020;30:269-271]

3. Sarilumab – A human monoclonal antibody against the interleukin-6 (IL-6) receptor, the host target for SARS-Cov-2, sarilumab is expected to lessen the overactive inflammatory response of the lungs by blocking the IL-6 receptor. Three clinical trials will test the efficacy and safety of sarilumab and remdesivir, a new investigational drug. [www.prnewswire. com/news-releases/regeneron-and-sanofi-begin-globalkevzara-sarilumab-clinical-trial-program-in-patients-withsevere-covid-19-301024752.html; www.news.sanofi.us/2020-03-16-Sanofiand-Regeneron-begin-global-Kevzara-R-sarilumabclinical-trial-program-in-patients-with-severe-COVID-19; www. clinicaltrialsarena.com/news/feinstein-institutes-covid-19- trials/]

4. Remdesivir – This antiviral drug was originally developed to fight the Ebola virus. Gilead Science recently published results of compassionate use of remdesivir, in which 30 of 61 severely ill COVID-19 patients on mechanical ventilation showed significant improvement and 17 were extubated. Twenty-five patients were discharged and seven died, of whom six were on invasive ventilation and one was not. [N Engl J Med 2020;doi:10.1056/NEJMoa2007016]

5. Darunavir – An antiviral drug used as HIV-1 protease inhibitor, darunavir demonstrates anti-SARS-CoV-2 activity in vitro in a test performed in China. It inhibited the viral replication at a concentration of 300 µM, but on 18 March 2020, Johnson and Johnson announced that there is no evidence to support the activity of darunavir against SARS-CoV-2. [www.sd.chinanews. com/2/2020/0205/70145.html]

6. Favipiravir – More popularly known as Avigan, favipiravir or T-705 was approved for the treatment of the influenza virus. It inhibits RNA-dependent RNA polymerase in RNA virus such as SARS-CoV-2. A preliminary trial in February was carried out on 80 patients and indicated better results for favipiravir than for lopinavir/ritonavir, with fewer adverse effects. Another clinical trial reported encouraging results with patients showing cleared viral load in 4 days as compared to 11 days in those receiving standard care only. Favipiravir was first developed by Fujifilm in Japan. [Antivir Res 2018;153:85-94; www.medicalnewstoday.com/articles/anti-flu-drug-effective-in-treating-covid-19; www.sciencedirect.com/science/article/pii/S2095809920300631]

7. Umifenovir – This drug demonstrates promising activity against SARS-CoV-2 in vitro by inhibiting the virus at concentration as low as 10–30 µM. In a randomized, open-labeled, multicentred clinical trial published on 20 March 2020, patients were assigned to receive either umifenovir or favipiravir. The 7 days’ recovery rate for umifenovir was 55.86 percent vs 71.43 percent for favipiravir (p=0.0199). [www.medrxiv.org/content/10.1101/2020.03.17.20037432v4]

8. Lopinavir/Ritonavir – The combination of lopinavir and ritonavir was approved for the treatment of HIV and was also found to have anti-SARS-CoV efficacy in vitro. However, a recent clinical trial on severe COVID-19 patients did not show any benefit when compared to standard care. No significant clinical improvement and no reduction in deaths were observed for those who received lopinavir/ritonavir. [Thorax 2004;59:252-256;
N Engl J Med 2020;doi:10.1056/NEJMoa2001282]

9. Interferon-α (IFN-α) – IFN-α is a broad-spectrum antiviral drug approved for treating viral hepatitis. It has been used to treat COVID-19 at a dose of 5 million units through vapour inhalation twice a day alone or in combination with ribavirin (500 mg 2–3 times a day) and lopinavir/ritonavir (400 mg/100 mg) for 10 days. Findings showed that SARS-CoV-2 is more susceptible to IFNs as compared to SARS-CoV as inhalation of IFN-α 2b lowered the infection rate. [Biosci Trends 2020;14:69-71;
Drug Discov Ther 2020;14:58-60; Antivir Res 2020;178:104791;
World J Pediatr 2020;doi:10.1007/s12519-020-00344-6]

10. Interferon-β (IFN-β) - IFN-β was developed for the treatment of chronic obstructive pulmonary disorder. A previous study reported that a decrease in IFN-β production is directly linked to increased susceptibility to severe respiratory diseases from viral infections. It was also observed that SARS-CoV-2 infection suppresses IFN-β production. A UK biotechnology firm has recently been given the go signal to conduct a trial using IFN-β on COVID-19 patients. [Antivir Res 2020;178:104791; www.pharmaceutical-technology.com/comment/synairgensng001-covid-19-trials/]

“Hopefully, we would be able to identify the most suitable approach to combat this deadly virus very soon and make this world a healthy place to live again,” the researchers said.

Use of corticosteroid is not associated with improved outcomes in idiopathic pulmonary fibrosis (IPF) patients admitted to the hospital with acute exacerbation (AE), reveals a recent study. In addition, corticosteroids may even contribute to reduced overall survival following exacerbation.

Acne is a common skin problem seen in primary care. Dr Wong
Soon Tee of Assurance Skin Clinic at Mt Elizabeth Novena Hospital, Singapore
shares his insights with Pearl Toh on how to manage acne in the primary care
setting.